U.S. patent application number 14/458344 was filed with the patent office on 2014-11-27 for device for in-vivo determination of eye moisture.
The applicant listed for this patent is Zvi NACHUM. Invention is credited to Zvi NACHUM.
Application Number | 20140350376 14/458344 |
Document ID | / |
Family ID | 45929982 |
Filed Date | 2014-11-27 |
United States Patent
Application |
20140350376 |
Kind Code |
A1 |
NACHUM; Zvi |
November 27, 2014 |
DEVICE FOR IN-VIVO DETERMINATION OF EYE MOISTURE
Abstract
A medical diagnostic device and method, the device including:
(a) an alternating current source, adapted to produce an
alternating current; (b) an electrode arrangement having at least
first and second electrodes, separated by an electrically
insulating region, the arrangement having an at least semi-rigid
region that fixes the electrodes in a spaced-apart manner, the
arrangement adapted to contact the soft tissue on the inner surface
of the eyelid; and (c) a processor, associated with the electrode
arrangement, said electrodes electrically connected to the
alternating current source; wherein, when the electrode arrangement
is provided with the alternating current, and is disposed against
the soft tissue, the soft tissue electrically bridges between the
electrodes to form an electrical circuit, wherein an electrical
signal is produced by the alternating current electrically passing
between the electrodes via the soft tissue; wherein the processor
is adapted to receive in-vivo based electrical information
originating from the electrical signal, via the circuit, and to
produce an output relating to, or derived from, the moisture
parameter, based on the in-vivo electrical information; and wherein
the processor is designed and configured to compute the moisture
parameter in the soft tissue, at least partially based on the
in-vivo electrical information, and based on an empirical
correlation between the in-vivo electrical information and the
moisture parameter.
Inventors: |
NACHUM; Zvi; (Tiberias,
IL) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
NACHUM; Zvi |
Tiberias |
|
IL |
|
|
Family ID: |
45929982 |
Appl. No.: |
14/458344 |
Filed: |
August 13, 2014 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
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PCT/IB2013/000173 |
Feb 12, 2013 |
|
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14458344 |
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Current U.S.
Class: |
600/383 |
Current CPC
Class: |
A61B 3/101 20130101;
A61B 5/053 20130101 |
Class at
Publication: |
600/383 |
International
Class: |
A61B 3/10 20060101
A61B003/10; A61B 5/053 20060101 A61B005/053 |
Foreign Application Data
Date |
Code |
Application Number |
Feb 13, 2013 |
GB |
GB1202387.5 |
Claims
1. A device for evaluation of a moisture characterization parameter
associated with moisture of soft tissue on an inner surface of an
eyelid of a subject, the device comprising: (a) an alternating
current source, adapted to connect to a power supply and to produce
an alternating current; (b) an electrode arrangement having at
least a first electrode and a second electrode, said first
electrode electrically separated from said second electrode by an
electrically insulating region, said arrangement having an at least
semi-rigid region fixing said electrodes in a spaced-apart manner,
said arrangement adapted to contact the soft tissue on the inner
surface of the eyelid, said electrodes and said insulating region
composed of biocompatible materials; and (c) a processor,
associated with said electrode arrangement, said first and second
electrodes being electrically connected to said alternating current
source, wherein, when said electrode arrangement is provided with
said alternating current, and is disposed against the soft tissue,
the soft tissue electrically bridges between said electrodes to
form an electrical circuit, such that an electrical signal is
produced by said alternating current passing from said first
electrode to said second electrode via the soft tissue, said
processor being adapted to receive in-vivo based electrical
information originating from said electrical signal, via said
circuit, and to produce an output relating to, or derived from, the
moisture parameter, based on said in-vivo electrical information,
said processor being designed and configured to compute the
moisture parameter in the soft tissue, at least partially based on
said in-vivo electrical information, and based on an empirical
correlation between said in-vivo electrical information and said
moisture parameter, said empirical correlation including an inverse
relationship between an electrical impedance derived from said
electrical signal or from said in-vivo electrical information, and
said moisture parameter, such that an increasing level of moisture
of soft tissue on the inner surface of the eyelid is correlated
with a decreasing of said electrical impedance.
2. The device of claim 1, said moisture parameter being, or
including, an eye-moisture characterization parameter selected from
the group of parameters consisting of a calculated in-vitro
osmolarity, a calculated Schirmer's Test absorption length, a
calculated Meibomian Grading Score, an ocular surface disease index
(OSDI), a corneal and conjunctival staining result, and an eye
dryness severity value.
3. The device of claim 1, further comprising an adaptor,
electrically connected to said alternating current source, said
adaptor having an engagement mechanism adapted to physically hold a
portion of said arrangement and to electrically connect said
arrangement to said current source and to said processor.
4. The device of claim 3, said engagement mechanism adapted to
releasably and reversibly engage said arrangement.
5. The device of claim 1, said arrangement including, or consisting
of, an electrode stick.
6. The device of claim 4, said engagement mechanism adapted to
releasably and reversibly engage said arrangement, said arrangement
including, or consisting of, an elongated electrode stick having a
first end adapted to be received by said engagement mechanism, and
a second end having said electrodes.
7. The device of claim 6, said second end having a maximum width of
6.5 mm or 6.3 mm.
8. The device of claim 6, said second end having a minimum width of
2 mm.
9. The device of claim 6, wherein a maximum distance between said
second end of said stick, and an end of said electrodes distal to
said second end, is 2.5 mm.
10. The device of claim 1, further comprising a capacitor,
electrically disposed between said electrode arrangement and said
processor, said capacitor having a capacitance to pass an output
signal to said processor, when said electrical signal is above a
pre-defined threshold.
11. The device of claim 3, wherein an end of said arrangement has
an attachment geometry that is complementary to an attachment
geometry of said engagement mechanism.
12. The device of claim 1, said electrodes being disposed on an at
least semi-rigid substrate.
13. The device of claim 12, said electrode arrangement having a
thickness, including said substrate, of less than 1.5 mm.
14. The device of claim 1, further comprising a display,
electrically associated with said processor, and adapted to display
said output.
15. The device of claim 1, further comprising a housing, said
processor and said alternating current source disposed within said
housing.
16. The device of claim 1, said processor adapted to calculate said
electrical impedance (Z) based on a relationship: Z=R+iX where R is
an ohmic resistance of said circuit and X is a reactance of said
circuit.
17. The device of claim 16, said reactance (X) consisting
substantially solely of a capacitance term (X.sub.c).
18. A method comprising: (a) providing the device according to
claim 1; (b) disposing a portion of the electrode arrangement on
the inner eyelid, against the soft tissue such that the soft tissue
electrically bridges between the electrodes to form said electrical
circuit; (c) passing said alternating current from said first
electrode to said second electrode via the soft tissue, to produce
said electrical signal; and (d) receiving, by said processor, said
electrical information originating from said electrical signal, via
said circuit.
19. The method of claim 18, further comprising computing, by said
processor, a representation of the parameter associated with the
moisture of the soft tissue, based on said in-vivo electrical
information, and based on an empirical correlation between said
electrical information and said moisture parameter.
20. The method of claim 18, said empirical correlation including an
inverse relationship between said moisture parameter and an
electrical impedance derived from said electrical signal or from
said in-vivo electrical information, such that an increasing level
of moisture of soft tissue on the inner surface of the eyelid is
correlated with a decreasing of said electrical impedance.
Description
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This application is a continuation-in-part of
PCT/IB2013/000173 titled "Device for In-Vivo Determination of Eye
Moisture" and filed on or around Feb. 12, 2013, which is
incorporated herein by reference in its entirety. This application
draws priority from UK Patent Application No. GB1202387.5, entitled
"Device for In-Vivo Determination of Eye Moisture", and filed Feb.
12, 2012, which application is hereby incorporated by reference for
all purposes as if fully set forth herein.
FIELD AND BACKGROUND OF THE INVENTION
[0002] The present invention relates to an instrument for
indirectly determining the moisture of soft tissue on an inner
surface of an eyelid of a patient.
[0003] Dry eye is recognized as a disturbance of the Lachrymal
Functional Unit, a system made up of the lachrymal glands, the
ocular surface (cornea, conjunctiva and meibomian glands) and lids.
This system further includes the sensory and motor nerves that
connect these components.
[0004] The dry eye phenomenon may result from inadequate tear
production: the lachrymal gland fails to produce sufficient tears
to keep the conjunctiva and cornea covered by a complete tear
layer. The dry eye phenomenon may also stem from an abnormal tear
composition, which causes an overly rapid evaporation of the tears.
Thus, while the tear gland produces a sufficient amount of tears,
the rate of evaporation is such that the entire surface of the eye
cannot be kept covered with a complete layer of tears in various
activities or environments.
[0005] Various means have been disclosed for diagnosing dry eye, or
more generally, the extent of moisture in the outer eye. Schirmer's
test determines whether the eye produces enough tears to keep it
moist. Paper strips, inserted in an outer region of the eye
(typically the lower eyelid), absorb the tear liquid. After several
minutes, the amount of liquid absorbed is measured. Based on the
amount of liquid absorbed, a determination may be made regarding
the dryness of the eye. The diagnostic reliability of Schirmer's
test has been the subject of scholarly debate, and many believe
that the test may systematically produce false "normal"
results.
[0006] In-vitro tear osmolarity, which indicates the concentration
of salts dissolved in the tear, has long been correlated with
dryness of the eye. Since the 1970's, increasing severity of eye
dryness has been correlated with increasing in-vitro tear
osmolarity (see Farris R L, "Tear osmolarity--a new gold standard?"
Adv Exp Med Biol 1994; 350:495-503).
[0007] Over the years, various techniques and systems have been
developed for removing tear liquid from the eye, and for subjecting
the liquid to in-vitro analysis. An exemplary commercial product is
the TearLab.TM. Osmolarity system (see Dr. G. N. Foulks et al.,
"TearLab.TM. Osmolarity as a Biomarker for Disease Severity in mild
to Moderate Dry Eye Disease", www.bon.de/download/tearlab/Summary
_poster.sub.--2009_AAO.pdf). The system is adapted to measure the
osmolarity of human tears for diagnosing dry eye disease. The tear
liquid is collected directly from the inferior lateral tear
meniscus. A single-use, disposable polycarbonate microchip contains
a microchannel at the tip, designed to collect 50 nanoliters (nL)
of tear fluid directly from the inferior meniscus of the ocular
surface. Gold electrodes embedded in the polycarbonate card enable
in-vitro measurement of the electrical impedance of the tear fluid
sample in the channel. The measured impedance is correlated to eye
dryness, and to measured eye dryness parameters of Schirmer's test
and other diagnostic measurement methods for determining dry
eye.
[0008] Table 1 of Foulks et al., provided as Table 1 hereinbelow,
shows typical values for various eye dryness diagnostic methods, as
a function of severity--Grade 0 to Grade 4, with Grade 4
representing the highest severity of dry eye disease.
TABLE-US-00001 TABLE 1 Grade 0 1 2 3 4 Schirmer Test (mm) 35 7 5 2
0 TBUT (seconds) 45 7 5 3 0 Staining (NEI/Industry scale) 0 3 8 12
20 OSDI 0 15 30 45 100 Meibomian Grading Score 0 5 12 20 28
Osmolarity (mOsms/L) 275 308 324 364 400
It is intuitively evident that in Schirmer's Test, tear absorption
length would be expected to decrease with increasing severity of
dry eye disease. Table 1 demonstrates this trend. Similarly, it
would be expected that the degree of salinity, or osmolarity, of
the tear liquid would increase with increasing severity of dry eye
disease. Table 1 also demonstrates this trend.
[0009] Foulks et al., statistically derive an equation correlating
osmolarity and severity of eye dryness. On a scale of 0 to 1 (where
1 represents the highest level of severity), the correlation
equation is given as:
SEVERITY=(y-275)/125
where y is the osmolarity in units of mOsms/L. It is clear from
Table 1 and from the correlation equation, that increasing
osmolarity is indicative of increasingly severe eye dryness.
[0010] U.S. Pat. No. 4,996,993, filed Dec. 7, 1988, discloses
several devices for determining in-vivo tear osmolarity in the open
eye. A first device, an osmometer, is adapted to measure the
osmolarity of a bodily fluid such as tears or sweat, and includes a
detachable probe in combination with means for measuring the
conductivity between two electrodes of the probe. The osmometer
further includes means for converting the measured value of
conductivity of the in-vivo sample into a corresponding value of
osmolarity and display means for displaying a visible
representation of that value.
[0011] A second device is adapted to measure, by means of a sensor,
some physical quantity (such as dew point temperature) related to
the vapor pressure from a bodily fluid. The device is mounted
inside a confining, generally concave shell placed adjacent to a
portion of the human body for a measurement to be made. To measure
tear osmolarity in the open eye, the confining shell could take the
form of a conventional eyecup. The sensor can be a thermocouple or
thermistor controlled by a microprocessor to measure vapor pressure
by the dew point depression method.
[0012] U.S. Pat. No. 4,996,993 fails to explicitly disclose the
basis for converting the measured value of conductivity of the
in-vivo sample into a corresponding value of osmolarity. However,
in studying U.S. Pat. No. 4,996,993, one of ordinary skill in the
art would appear to derive some guidance from that patent's
reference to a relevant journal article, and to the patent's
treatment thereof: [0013] The particular pathologic condition
designated "dry eye" and its connection to tear film osmolarity is
described in the article "Osmolarity of Tear Microvolumes in
Keratoconjunctivitis Sicca," by Jeffrey P. Gilbard et al., in Arch.
Ophthalmol., Vol. 96, April, 1978, pages 677-681. When the surface
of the eye starts to dry out the tear film becomes hypertonic
(elevated osmolarity), causing discomfort and epithelial damage.
Thus, although U.S. Pat. No. 4,996,993 fails to provide an explicit
relationship between in-vivo measurement of conductivity and tear
liquid osmolality, it is fairly understood that higher conductivity
(or lower impedance) measurements are correlated with eye dryness,
as taught by Gilbard et al., the above-referenced Farris article
(which also references and supports the findings of Gilbard), and
as confirmed and detailed in the recent study of Foulks et al.,
referenced above.
[0014] In "Electrical conductivity of tear fluid in healthy persons
and keratoconjunctivitis sicca patients measured by a flexible
conductimetric sensor" [Graefe's Arch Clin Exp Ophthalmol (1996)
234:542-546], Ogasawara et al. disclose a flexible conductimetric
sensor that is small enough and flexible enough to be placed on the
ocular surface to measure the electrical conductivity of tear fluid
in vivo. The sensitive area of the sensor was placed within the
lower temporal conjunctival cul-de-sac. The conductivity was
measured continuously for more than 30 seconds. The sodium chloride
concentration of tear fluids was calculated from a calibration
curve relating electrical conductivity (Siemens) to the NaCl
concentration (g/l), and converted to the equivalent electrolyte
concentration.
[0015] The average electrolyte concentration of 33 samples obtained
from 17 healthy persons was 296.4 mEq/l. The electrolyte
concentration in 29 samples obtained from keratoconjunctivitis
sicca patients averaged 324.8 mEq/l. The difference was found to be
statistically significant.
[0016] The above-described advances notwithstanding, the present
inventor has recognized a need for improved, patient-friendly,
cost-effective devices and methods for evaluating the moistness or
dryness in the vicinity of the outer eye, and the subject matter of
the present disclosure and claims is aimed at fulfilling this
need.
SUMMARY OF THE INVENTION
[0017] According to the teachings of the present invention there is
provided a device for evaluation of a moisture parameter associated
with moisture of soft tissue on an inner surface of an eyelid of a
subject, the device including: (a) an alternating current source,
adapted to connect to a power supply and to produce an alternating
current; (b) an electrode arrangement having at least a first
electrode and a second electrode, the first electrode electrically
separated from the second electrode by an electrically insulating
region, the arrangement having an at least semi-rigid region that
fixes the electrodes in a spaced-apart manner, the arrangement
adapted to contact the soft tissue on the inner surface of the
eyelid, the electrodes and the insulating region composed of
biocompatible materials, and (c) a processor, associated with the
electrode arrangement, the first and second electrodes being
electrically connected to the alternating current source; wherein,
when the electrode arrangement is provided with the alternating
current, and is disposed against the soft tissue, the soft tissue
electrically bridges between the electrodes to form an electrical
circuit, wherein an electrical signal is produced by the
alternating current passing from the first electrode to the second
electrode via the soft tissue, wherein the processor is adapted to
receive in-vivo based electrical information originating from the
electrical signal, via the circuit, and to produce an output
relating to, or derived from, the moisture parameter, based on the
in-vivo electrical information, and wherein the processor is
designed and configured to compute the moisture parameter in the
soft tissue, at least partially based on the in-vivo electrical
information, and based on an empirical correlation between the
in-vivo electrical information and the moisture parameter.
[0018] According to another aspect of the present invention there
is provided a method for evaluating a parameter associated with
moisture of soft tissue of an inner eyelid of a subject, the method
including: (a) providing a device including: (i) an alternating
current source, adapted to connect to a power supply and to produce
an alternating current; (ii) an electrode arrangement having at
least a first electrode and a second electrode, the first electrode
electrically separated from the second electrode by an insulating
region, the arrangement having an at least semi-rigid region that
fixes the electrodes in a spaced-apart manner, the arrangement
adapted to contact the soft tissue of the inner eyelid of the
subject, (iii) a processor, associated with the electrode
arrangement; wherein the first and second electrodes are
electrically connected to the alternating current source, (b)
disposing a portion of the electrode arrangement on the inner
eyelid, against the soft tissue, wherein the soft tissue
electrically bridges between the electrodes to form an electrical
circuit, (c) passing the alternating current from the first
electrode to the second electrode via the soft tissue, producing an
electrical signal; (d) receiving, by the processor, electrical
information originating from the electrical signal, via the
circuit, and (e) computing, by the processor, a representation of
the parameter associated with the moisture of the soft tissue,
based on the electrical information.
[0019] According to yet another aspect of the present invention
there is provided a method for evaluating a parameter associated
with moisture of soft tissue of an inner eyelid of a subject, the
method including (a) providing a device substantially as described
herein; (b) disposing a portion of the electrode arrangement on the
inner eyelid, against the soft tissue such that the soft tissue
electrically bridges between the electrodes to form said electrical
circuit; (c) passing said alternating current from said first
electrode to said second electrode via the soft tissue, to produce
said electrical signal; and (d) receiving, by said processor, said
electrical information originating from said electrical signal, via
said circuit.
[0020] According to further features in the described preferred
embodiments, the method further includes computing, by said
processor, the parameter, or a representation of the parameter,
associated with the moisture of the soft tissue, based on the
in-vivo electrical information, and based on an empirical
correlation between the electrical information and the moisture
parameter.
[0021] According to still further features in the described
preferred embodiments, the empirical correlation includes an
inverse relationship between the electrical impedance derived from
the electrical signal or from the in-vivo electrical information,
and the moisture parameter, such that an increasing level of
moisture of soft tissue on the inner surface of the eyelid is
correlated with a decreasing of the electrical impedance.
[0022] According to still further features in the described
preferred embodiments, the empirical correlation includes a direct
relationship between an electrical conductivity derived from the
electrical signal or from the in-vivo electrical information, and
the moisture parameter, whereby an increasing level of moisture of
soft tissue on the inner surface of the eyelid is correlated with a
decreasing of the electrical conductivity.
[0023] According to still further features in the described
preferred embodiments, the in-vivo electrical information consists
of measured in-vivo electrical information.
[0024] According to still further features in the described
preferred embodiments, the device further includes a display,
electrically associated with the processor, and adapted to display
the output.
[0025] According to still further features in the described
preferred embodiments, the device further includes an adaptor,
electrically connected to the alternating current source, the
adaptor having an engagement mechanism adapted to physically hold a
portion of the arrangement and to electrically connect the
arrangement to the current source and to the processor.
[0026] According to still further features in the described
preferred embodiments, the engagement mechanism is adapted to
releasably and reversibly engage the arrangement.
[0027] According to still further features in the described
preferred embodiments, the arrangement includes, or consists of, an
electrode stick.
[0028] According to still further features in the described
preferred embodiments, the electrode stick is an elongated stick
having a first end adapted to be received by the engagement
mechanism, and a second end having the electrodes.
[0029] According to still further features in the described
preferred embodiments, the second end has a maximum width of 6.5
mm, 6.3 mm, 6.2 mm, or 6 mm.
[0030] According to still further features in the described
preferred embodiments, the second end has a minimum width of 2
mm.
[0031] According to still further features in the described
preferred embodiments, the maximum distance between the second end
of the stick, and an end of the electrodes distal to the second
end, is 2.5 mm, 2.2 mm, 2 mm, 1.9 mm or 1.8 mm.
[0032] According to still further features in the described
preferred embodiments, the device further includes an
analog-to-digital conversion unit, electrically connected to the
electrical circuit, and adapted to convert the electrical signal
from an analog form to a digital form.
[0033] According to still further features in the described
preferred embodiments, the device further includes a display,
electrically associated with the processor, and adapted to display
the moisture parameter.
[0034] According to still further features in the described
preferred embodiments, the device further includes a capacitor,
electrically disposed between the electrode arrangement and the
processor, the capacitor having a capacitance to pass an output
signal to the processor, when the electrical signal is above a
pre-defined threshold.
[0035] According to still further features in the described
preferred embodiments, the end of the electrode arrangement has an
attachment geometry that is complementary to an attachment geometry
of the engagement mechanism.
[0036] According to still further features in the described
preferred embodiments, the electrodes are disposed on an at least
semi-rigid substrate.
[0037] According to still further features in the described
preferred embodiments, the thickness of the electrode arrangement,
including the substrate, is less than 1.5 mm, less than 1.2 mm,
less than 1.0 mm, less than 0.8 mm, or less than 0.6 mm.
[0038] According to still further features in the described
preferred embodiments, the moisture parameter is, or includes, an
eye-moisture characterization parameter selected from the group of
parameters consisting of a calculated in-vitro osmolarity, a
calculated Schirmer's Test absorption length, a calculated
Meibomian Grading Score, an ocular surface disease index (OSDI), a
corneal and conjunctival staining result, and an eye dryness
severity value.
BRIEF DESCRIPTION OF THE DRAWINGS
[0039] The invention is herein described, by way of example only,
with reference to the accompanying drawings. With specific
reference now to the drawings in detail, it is stressed that the
particulars shown are by way of example and for purposes of
illustrative discussion of the preferred embodiments of the present
invention only, and are presented in the cause of providing what is
believed to be the most useful and readily understood description
of the principles and conceptual aspects of the invention. In this
regard, no attempt is made to show structural details of the
invention in more detail than is necessary for a fundamental
understanding of the invention, the description taken with the
drawings making apparent to those skilled in the art how the
several forms of the invention may be embodied in practice.
Throughout the drawings, like-referenced characters are used to
designate like elements.
[0040] In the drawings:
[0041] FIG. 1 is a perspective view of one aspect of the in-vivo
eye moisture determination device, according to the present
invention;
[0042] FIG. 2 shows the inventive device being used to make an
in-vivo eye moisture determination, the electrode stick being
contacted with the moist tissue of the inner eyelid;
[0043] FIG. 3 is an exemplary graph plotting measured Schirmer's
Test absorption depth as a function of in-vivo measured
impedance;
[0044] FIG. 4A provides (1): a graph plotting in-vitro measured
impedance of solutions as a function of NaCl concentration, based
on Ogasawara et al.; and (2) an exemplary graph plotting in-vivo
measured impedance of solutions, using a device and method of the
present invention, as a function of the correlated NaCl
concentration;
[0045] FIG. 4B is an exemplary graph plotting calculated in-vitro
osmolarity as a function of in-vivo measured impedance;
[0046] FIG. 5 is a schematic block diagram of one aspect of the
in-vivo eye moisture determination device, according to the present
invention;
[0047] FIG. 6a is a schematic block diagram of an electrode
arrangement or stick, according to one embodiment of the present
invention;
[0048] FIG. 6b provides a schematic, perspective view of the
electrode stick of FIG. 6a, disposed, at one end, within a
receptacle of the inventive device; and
[0049] FIG. 7 is a logical flow diagram showing one aspect of the
method of the present invention.
DETAILED DESCRIPTION OF THE ILLUSTRATED EMBODIMENTS
[0050] The principles and operation of the inventive instrument for
evaluating the moistness or dryness in the vicinity of the outer
eye may be better understood with reference to the drawings and the
accompanying description.
[0051] Before explaining at least one embodiment of the invention
in detail, it is to be understood that the invention is not limited
in its application to the details of construction and the
arrangement of the components set forth in the following
description or illustrated in the drawings. The invention is
capable of other embodiments or of being practiced or carried out
in various ways. Also, it is to be understood that the phraseology
and terminology employed herein is for the purpose of description
and should not be regarded as limiting.
[0052] Referring now to the drawings, FIG. 1 is a perspective view
of one aspect of an in-vivo eye moisture determination device 100,
according to the present invention. From a first end of an
elongated housing 101 extends a receptacle or adaptor 125 for
physically and electrically receiving an electrode stick (shown in
FIG. 2, and shown schematically in FIG. 6b). At a distal end of
housing 101 may be disposed a battery or power source 104. A switch
128 may advantageously be disposed on a facing of housing 101, for
facile activation and deactivation of device 100. An electrode
stick switch 129 for locking and releasing the stick from adaptor
125 may similarly be disposed on a facing of housing 101.
[0053] In describing an in-vivo, conductivity-based device for
assessing eye dryness, U.S. Pat. No. 4,996,993 teaches that the
"distal ends 24A and 24B of electrodes 26 and 28, respectively, end
in blunt shapes suitable for touching delicate parts of the body
such as the cornea". I have found, however, that directly
contacting an electrical probe with the cornea raises patient
safety issues. The measurements made may be unreliable, due to poor
contact conditions, and the low amount of liquid natively disposed
on the cornea. The impact on reliability of voluntary and
involuntary motions of the patient, due to pain, discomfort, or
apprehension, cannot be underestimated. Moreover, such unreliable
results may be made even less reliable by the procedures used by
each particular medical personnel operating the conductivity-based
device, and by their medical concerns pertaining to causing damage
to the sensitive and delicate regions of the eye.
[0054] I have also found that disposing an electrical probe within
the lower temporal conjunctival cul-de-sac, as taught by Ogasawara
et al., may raise various patient safety issues. Some of these
issues may be even more severe in view of the lengthy measuring
time of more than 30 seconds.
[0055] FIG. 2 shows the inventive device being used to make an
in-vivo eye moisture determination, the electrode stick being
contacted with the moist tissue of the inner eyelid. It will be
appreciated that there exists a finite and significant distance
between the end of the electrode stick and the delicate outer
surface of the eye, which enables medical personnel to practice the
procedure of the instant invention in a safe and substantially
repeatable fashion.
[0056] However, I have found that having a safe and substantially
repeatable testing procedure, while being necessary, may be
insufficient in obtaining repeatable and physically meaningful
results.
[0057] I tested electrode sticks of various widths on the inner
surface of the lower eyelid of a particular subject. The results
are provided in Table 2. The widest stick, 8 mm did not display
good repeatability. This may be attributed to large and varying
areas of the electrode that are not fully immersed in the tear
liquid. The stick having an intermediate width of 6.2 mm displayed
improved repeatability. However, the electrode stick having a width
of 3.9 mm exhibited, by far, the best repeatability
performance.
[0058] Thus, the electrode sticks of the present invention may have
a width of at most 6.5 mm, at most 6.3 mm, at most 6 mm, at most
5.7 mm, at most 5.5 mm, at most 5.25 mm, at most 5 mm, or at most
4.75 mm. It may be preferable for the width to be at most 4.5 mm,
at most 4.25 mm, or at most 4.0 mm.
TABLE-US-00002 TABLE 2 Trial No. 8 mm 6.2 mm 3.9 mm 1 2.56 3.79
5.20 2 2.78 3.90 5.21 3 3.59 3.50 5.29 4 error 4.23 5.15 5 5.66
4.44 5.17
[0059] Various considerations including practical considerations,
may dictate, or at least indicate, a minimum stick width of 2 mm,
2.25 mm, or 2.5 mm.
[0060] We have further found that the soft tissue on the inner
surface of the eyelid, and more practically, on the inner surface
of the lower eyelid, displays an electrical behavior having both a
resistance component and a capacitance component. Direct current is
suitable for measuring the resistance component, but may be
unsuitable for measuring the capacitance component. However, an
alternating current source is suitable for measuring both the
resistance component and the capacitance component. The frequency
of the alternating current source is preferably between 100-15,000
Hz, more preferably, between 300-10,000 Hz, and most preferably,
between 500-5,000 Hz.
[0061] Using such an alternating current source, we tested the
in-vivo impedance on the inner surface of the lower eyelid of
subjects having a varying degree of eye moisture. These individuals
were further subjected to a conventional Schirmer's Test in the
same eye. The results are provided in Table 3, and are graphically
displayed in FIG. 3. Surprisingly, we observe an increase in-vivo
measured impedance with decreasing eye moisture (as physically
measured by Schirmer's Test, and as correlated with in vitro
osmolality and with the corresponding NaCl concentration). We have
found the correlation of increasing in-vivo measured impedance with
decreasing eye moisture to be repeatable. Moreover, this
correlation runs opposite and contrary to the well-established,
above-described and referenced correlation between increasing
in-vitro measured impedance (decreasing electrical conductivity)
and increasing eye moisture.
TABLE-US-00003 TABLE 3 Measured In-Vivo Schirmer's Test:
Correlated.sup.1 Correlated.sup.2 NaCl Impedance Measured
Osmolality Concentration (kiloohms) Absorption (mm) (mOsms/L) (g/L)
3.6 35 275 8.61 5.1 20 5.4 15 6.7 12 6.5 7 8.6 2 9.2 1 11 0 400
12.684 .sup.1Foulks, et al. .sup.2based on Horatio Papa Ph.D.:
USP29, page 2718
(http://www.pharmacopeia.cn/v29240/usp29nf24s0_c785.html#usp29nf24s0_c785-
-t1)
[0062] In FIG. 4A is provided a graph plotting in-vitro measured
impedance of solutions as a function of sodium chloride
concentration, based on data of the prior art (Ogasawara et al.).
FIG. 4A further provides an exemplary graph plotting in-vivo
measured impedance of solutions, using a device and method of the
present invention, as a function of the correlated sodium chloride
concentration.
[0063] It is manifest from FIG. 4A that the correlation of eye
moisture to impedance, using the device and method of the present
invention, displays a higher sensitivity to impedance than the
correlation of the prior art devices and methods. Perhaps more
importantly, the correlation is--surprisingly--reversed.
[0064] Without wishing to be limited by theory, I believe that the
decreasing eye moisture with increasing in-vivo measured impedance
may at least partly be attributed to liquidless areas or pockets in
the inner surface of the eyelid. As the eye becomes increasingly
dry, such pockets take up an increasing fraction of the surface
area of the electrodes, and reduce electrical conductivity/increase
impedance. This phenomenon more than compensates for the increased
conductivity/decreased impedance resulting from the higher salinity
of the tear liquid in dry eyes.
[0065] I believe it is highly surprising that the in-vivo measured
impedance exhibits an inverse behavior with respect to in-vitro
measured impedance, as a function of eye moisture. I believe it is
further surprising that the in-vivo measured impedance levels are
sufficiently repeatable, for a given extent of eye moisture, to
enable in-vivo impedance to be used as a marker for eye moisture
determination, particularly in view of the decreased impedance
resulting from the higher salinity of the tear liquid in dry
eyes.
[0066] The in-vivo measured impedance results may be correlated to
any known measure, qualitative or quantitative, of eye moisture or
eye dryness, including in-vitro osmolarity or osmolality,
Schirmer's Test, Meibomian Grading Score, ocular surface disease
index (OSDI), corneal and conjunctival staining, various eye
dryness severity scales. These results produce calculated
correlations, much as Foulks et al. produce correlation equations
to calculate, from measured in-vitro impedance/osmolarity,
equivalent eye dryness values using other eye dryness determination
methods.
[0067] In FIG. 4B is provided an exemplary graph plotting
calculated in-vitro osmolarity as a function of in-vivo measured
impedance.
[0068] FIG. 5 is a schematic block diagram of one aspect of a
device such as moisture-analyzing device 100, according to the
present invention. Moisture-analyzing device 100 includes a current
source such as alternating current source 102, connected to a power
supply 104 and adapted to produce an alternating current, and an
electrode arrangement 110 having at least a first electrode 112 and
a second electrode 114 set apart at a fixed distance. First
electrode 112 is electrically separated from second electrode 114
by an insulating region 120 having a specific electrical
resistivity of at least 1.0 ohm cm, and more typically, at least
10.sup.4 ohm cm or even 10.sup.6 ohm cm. Presently preferred
materials for insulating region 120 include various biocompatible
materials, including polymeric materials such as polypropylene and
polycarbonates.
[0069] Electrode arrangement 110 has a first lead 122 from first
electrode 112 and a second lead 124 from second electrode 114,
first lead 122 being electrically connected to alternating current
source 102. Electrode arrangement 110 may advantageously be
connected to alternating current source 102 by means of an adaptor
or receptacle 125, which will be described in greater detail
hereinbelow.
[0070] Electrode arrangement 110 is also electrically connected to
a processor, such as central processing unit (CPU) 150. CPU 150 is
adapted to receive electrical information originating from the
electrical signal, via an electrical circuit 190, and to compute a
representation of the level of moisture (or severity of dryness) in
the soft tissue of the inner eyelid of the subject, based on the
electrical information. To this end, a voltage-measuring device,
such as voltmeter 156, may advantageously be disposed on circuit
190, or within processor 150, to measure a voltage of the
electrical signal or information.
[0071] Second lead 124 may be electrically disposed between second
electrode 114 and CPU 150. Both current source 102 and second
electrode 114 may be connected to a ground 128.
[0072] Within, or otherwise electrically associated with CPU 150,
may be provided a memory unit 151 adapted to store data, e.g., data
pertaining to electrical parameters, to individual or collective
patient parameters or history, etc. Electrically associated with
CPU 150 may be a display unit 152 and an input unit 154. Display
unit 152, which may be of various types known in the art, including
LED and LCD displays, may display an output from CPU 150, such as a
calculated impedance between first electrode 112 and second
electrode 114, or a correlated level of moisture or dryness in the
outer vicinity of the subject's eye. This correlated level may be
expressed as the calculated in-vitro osmolality (or osmolarity)
equivalent, the calculated Schirmer's test equivalent, calculated
eye-dryness severity scale (0 to 4, 0 to 1, etc.), or any other
moisture-related or dryness-related expression that would be known
to one of ordinary skill in the art.
[0073] Input unit 154 may be of various types known in the art, and
may be used to select display options, and to provide information
to CPU 150. Such information may include data on a particular
patient undergoing the test, or the identity of the particular
patient.
[0074] Electrode arrangement 110 may also be electrically connected
to a capacitor 130, which serves to filter currents that are below
a pre-determined threshold. A filter such as low pass filter 140
may also be electrically connected to capacitor 130, to filter
currents that are above a pre-determined threshold.
[0075] The electrical signal from electrode arrangement 110 may be
an analog signal, which is converted to a digital signal by means
of an analog-to-digital (A2D) converter 145. (A2D) converter 145
may be disposed within CPU 150, or outside CPU 150, as shown. The
digital signal is then provided to a processing unit of CPU
150.
[0076] When electrode arrangement 110 is disposed against soft
tissue on an inner surface of the eyelid, the soft tissue
electrically bridges between the electrodes to complete electrical
circuit 190. The resulting output signal is provided to CPU 150 via
electrical circuit 190.
[0077] Preferably, the current source of electrical circuit 190 is
an alternating current source such as alternating current source
102.
[0078] A secondary, control circuit 195, may be advantageous in
controlling the parameters of alternating current source 102 within
working limits. Secondary circuit 195 may include CPU 150 and
alternating current source 102, along with a low pass filter 160
and a resistor 170 disposed therebetween, to facilitate correction
and control of alternating current source 102 by CPU 150.
[0079] FIG. 6a is a schematic top view of a preferred embodiment of
electrode stick or electrode arrangement 110. Electrode arrangement
110 may include a thin, at least semi-rigid substrate 232,
typically in the form of a stick or plate, for carrying electrodes
112, 114. It may be advantageous for substrate 232 to exhibit
flexibility, at least along a wide face thereof, so as to
substantially conform to an inner surface of the eyelid. However,
insulating region 120 must be sufficiently rigid to maintain the
electrodes in a substantially fixed, spaced-apart position.
[0080] Presently preferred materials for substrate 232 include
various biocompatible materials, including polymeric materials such
as polypropylene and polycarbonates.
[0081] Electrodes 112, 114 are advantageously made of a highly
conducting, biocompatible material such as gold, platinum, copper,
silver, as well as various alloys and mixtures containing such
materials.
[0082] Receptacle 125 may both mechanically and electrically
connect electrode arrangement 110 to alternating current source
102. FIG. 6b provides a schematic perspective view of electrode
arrangement 110 and receptacle 125 according to an exemplary,
preferred embodiment. A first end 234 of substrate 232 engages with
an engagement surface of receptacle 125. In FIG. 6b, first end 234
of substrate 232 is received by the engagement surface, which may
be substantially complementary to at least a portion of first end
234. A portion of the engagement surface may exert a pressure on
first end 234 of substrate 232 to fix electrode arrangement 110 in
place. Other connecting mechanisms for securing substrate 232 to
receptacle 125 will be apparent to those skilled in the art of
mechanical connection.
[0083] Receptacle 125 may attach to alternating current source 102
via a continuation of second lead 124 (not shown).
[0084] It will be appreciated that various hand-held,
impedance-measuring devices are known in the art, and are
commercially available. Hence, the description of the known aspects
of such a device has been broadly presented. One of ordinary skill
in the art will readily appreciate that various designs are
possible. Thus, the instant details of construction and the
arrangement of the components are not intended to limit the
application of the inventive device.
[0085] One aspect of the method of the present invention will now
be described, with reference to the logical flow diagram provided
in FIG. 7 (all numbered device components appear in FIG. 5). Using
a device such as moisture-analyzing device 100, an electrode
arrangement such as electrode arrangement 110 is disposed against
soft tissue of the inner eyelid (step 1). When alternating current
source 102 is activated, the soft tissue between and generally
around the electrodes electrically bridges between the electrodes
to complete electrical circuit 190. The alternating current passes
from the first electrode to the second electrode via the soft
tissue, producing an electrical signal (step 2).
[0086] Processor or CPU 150 receives this signal, or electrical
information derived from the electrical signal, via circuit 190
(step 3), and then processes the electrical signal, possibly along
with other information, to produce an output relating to, or
derived from, the parameter associated with soft tissue of the
inner eyelid of the subject (step 4). This eye-moisture correlated
output may then be displayed (step 5) by display unit 152.
[0087] The output may be in the form of a level of moisture or
moisture rating in the soft tissue of the inner eyelid, or in
various other forms. The output may be essential in diagnosing
various health conditions of the patient, and in assessing the
severity of various health problems. Also, the output may aid in
the matching of interventions and treatments to the true state of
the patient.
[0088] Processor 150 may calculate the electrical impedance (Z)
based on the relationship:
Z=R+iX
where R is the ohmic resistance and X is the reactance. In the eye,
we have found that the reactance term stems solely from
capacitance, hence,
Z=R+iX.sub.c
where X.sub.c is the capacitance of the circuit between the
electrodes.
[0089] The capacitance term is non-zero, and may appreciably
contribute to the electrical impedance.
[0090] In any event, when processor 150 is provided with the
current (I) provided by alternating current source 102, along with
a voltage signal from circuit 190, the impedance may be calculated
from the ratio of the two, according to the relationship:
Z=V/I
where V is a voltage associated with the voltage signal. The ratio
of voltage to current has been found to strongly correlate with
tissue moisture.
[0091] In monitoring the moisture of the tissue over the course of
time, we surprisingly found that when the electrode arrangement is
provided with the alternating current, and is disposed against the
soft tissue of the inner eyelid, the output signal is largely
unaffected by the particular time that the electrical measurement
is made, or by the length of time (at least within 2-10 seconds)
that the electrode stick is disposed against the soft tissue. The
impedance/conductivity measurements may be made over 10 times, over
20 times, over 50 times, or over 100 times, within the measurement
period, which is typically 2-10 seconds, and more typically, 3.5 to
7 seconds. The processor may thus be configured to provide an
average of the multiple readings, such that the result may be
appreciably more reliable than any individual reading. The
processor may be configured to eliminate faulty readings from the
average, or to weight the individual results obtained.
[0092] Thus, the device and method of the present invention may
provide results that are accurate, repeatable, and representative
of the state of moisture in the outer eye of the subject.
[0093] Processor 150 may use the relationship between voltage and
current to compute an absolute tissue moisture, or a relative
tissue moisture. The relative tissue moisture may be rated, by way
of example, on a scale of 1 to 10, or by comparison to the tissue
moistures for a particular group, e.g., based on gender.
[0094] As used herein in the specification and in the claims
section that follows, the terms "osmolarity" and "osmolality" are
used interchangeably. In the extremely weak saline tear solutions,
the difference between the terms is substantially negligible.
[0095] As used herein in the specification and in the claims
section that follows, the term "electrically connected" refers to a
physical connection between elements that enables an electrical
current to flow therebetween, when the elements are connected to a
current source delivering current.
[0096] It will be appreciated that certain features of the
invention, which are, for clarity, described in the context of
separate embodiments, may also be provided in combination in a
single embodiment. Conversely, various features of the invention,
which are, for brevity, described in the context of a single
embodiment, may also be provided separately or in any suitable
sub-combination.
[0097] Although the invention has been described in conjunction
with specific embodiments thereof, it is evident that many
alternatives, modifications and variations will be apparent to
those skilled in the art. Accordingly, it is intended to embrace
all such alternatives, modifications and variations that fall
within the spirit and broad scope of the appended claims. All
publications, patents and patent applications mentioned in this
specification are herein incorporated in their entirety by
reference into the specification, to the same extent as if each
individual publication, patent or patent application was
specifically and individually indicated to be incorporated herein
by reference. In addition, citation or identification of any
reference in this application shall not be construed as an
admission that such reference is available as prior art to the
present invention.
* * * * *
References